Evolution of Escherichia coli strains under competent and compromised immunity

Escherichia coli is a commensal of the intestine of most mammals, but also an important human pathogen. Within a healthy human its population structure is highly dynamic, where typically a dominant E. coli strain is accompanied by several low abundance satellite strains. However, the factors underlying E. coli strain dynamics and their evolution within hosts are still poorly understood. Here, we colonised germ-free immune-competent (wild-type) or immune-compromised (Rag2KO) mice, with two phylogenetically distinct strains of E. coli, to determine how strain co-existence and within-strain evolution are shaped by the adaptive immune system. We find that, in both WT and Rag2KO mice, one strain reaches a 100-fold larger abundance than the other. The abundance of the dominant strain is significantly higher in Rag2KO than in WT mice, and even under continued accumulation of beneficial mutations the strains co-exist for more than three thousand generations. Pool-sequencing of evolving clones revealed that the rates of mutation accumulation were significantly higher in immune-compromised than in immune-competent mice in the initial period of evolution. Furthermore, we identified adaptative mutations in the dominant strain specific to immune-competent mice that alter the survival-persistence-nutritional-competence (SPANC) trade-off of E. coli.